Cytologic atypia in the contralateral unaffected breast is related to parity and estrogen-related genes

Denise A. Monahan, Jun Wang, Oukseub Lee, Elizabeth Revesz, Nancy Taft, David Ivancic, Nora M. Hansen, Kevin P. Bethke, C. Zalles, Seema A. Khan*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Purpose The contralateral unaffected breast (CUB) of women with unilateral breast cancer provides a model for the study of breast tissue-based risk factors. Using random fine needle aspiration (rFNA), we have investigated hormonal and gene expression patterns related to atypia in the CUBs of newly diagnosed breast cancer patients. Methods 83 women underwent rFNA of the CUB. Cytologic analysis was performed using the Masood Score (MS), atypia was defined as MS > 14. RNA was extracted using 80% of the sample. The expression of 20 hormone related genes was quantified using Taqman Low Density Arrays. Statistical analysis was performed using 2-tailed t tests and linear regression. Results Cytological atypia was more frequent in multiparous women (P = 0.0392), and was not associated with any tumor-related features in the affected breast. Masood Score was higher with shorter interval since last pregnancy (R = 0.204, P = 0.0417), higher number of births (R = 0.369, P = 0.0006), and estrogen receptor (ER) negativity of the index cancer (R = −0.203, P = 0.065). Individual cytologic features were associated with aspects of parity. Specifically, anisonucleosis was correlated with shorter interval since last pregnancy (R = 0.318, P = 0.0201), higher number of births (R = 0.382, P = 0.0004), and ER status (R = −0.314, P = 0.0038). Eight estrogen-regulated genes were increased in atypical samples (P < 0.005), including TFF1, AGT, PDZK1, PGR, GREB1, PRLR, CAMK2B, and CCND1. Conclusions Cytologic atypia, and particularly anisonucleosis, is associated with recent and multiple births and ER negative status of the index tumor. Atypical samples showed increased expression of estrogen-related genes, consistent with the role of estrogen exposure in breast cancer development.

Original languageEnglish (US)
Pages (from-to)449-456
Number of pages8
JournalSurgical Oncology
Volume25
Issue number4
DOIs
StatePublished - Dec 1 2016

Fingerprint

Parity
Estrogens
Breast
Estrogen Receptors
Fine Needle Biopsy
Genes
Parturition
Breast Neoplasms
Multiple Birth Offspring
Pregnancy
Neoplasms
Linear Models
Hormones
RNA
Gene Expression

Keywords

  • Anisonucleosis
  • Breast cancer risk
  • Contralateral unaffected breast
  • Cytologic atypia
  • Gene expression
  • Random fine needle aspiration

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

@article{06a4fdfb587a4b0bac4a5022c6d1c2e9,
title = "Cytologic atypia in the contralateral unaffected breast is related to parity and estrogen-related genes",
abstract = "Purpose The contralateral unaffected breast (CUB) of women with unilateral breast cancer provides a model for the study of breast tissue-based risk factors. Using random fine needle aspiration (rFNA), we have investigated hormonal and gene expression patterns related to atypia in the CUBs of newly diagnosed breast cancer patients. Methods 83 women underwent rFNA of the CUB. Cytologic analysis was performed using the Masood Score (MS), atypia was defined as MS > 14. RNA was extracted using 80{\%} of the sample. The expression of 20 hormone related genes was quantified using Taqman Low Density Arrays. Statistical analysis was performed using 2-tailed t tests and linear regression. Results Cytological atypia was more frequent in multiparous women (P = 0.0392), and was not associated with any tumor-related features in the affected breast. Masood Score was higher with shorter interval since last pregnancy (R = 0.204, P = 0.0417), higher number of births (R = 0.369, P = 0.0006), and estrogen receptor (ER) negativity of the index cancer (R = −0.203, P = 0.065). Individual cytologic features were associated with aspects of parity. Specifically, anisonucleosis was correlated with shorter interval since last pregnancy (R = 0.318, P = 0.0201), higher number of births (R = 0.382, P = 0.0004), and ER status (R = −0.314, P = 0.0038). Eight estrogen-regulated genes were increased in atypical samples (P < 0.005), including TFF1, AGT, PDZK1, PGR, GREB1, PRLR, CAMK2B, and CCND1. Conclusions Cytologic atypia, and particularly anisonucleosis, is associated with recent and multiple births and ER negative status of the index tumor. Atypical samples showed increased expression of estrogen-related genes, consistent with the role of estrogen exposure in breast cancer development.",
keywords = "Anisonucleosis, Breast cancer risk, Contralateral unaffected breast, Cytologic atypia, Gene expression, Random fine needle aspiration",
author = "Monahan, {Denise A.} and Jun Wang and Oukseub Lee and Elizabeth Revesz and Nancy Taft and David Ivancic and Hansen, {Nora M.} and Bethke, {Kevin P.} and C. Zalles and Khan, {Seema A.}",
year = "2016",
month = "12",
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doi = "10.1016/j.suronc.2015.12.001",
language = "English (US)",
volume = "25",
pages = "449--456",
journal = "Surgical Oncology",
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Cytologic atypia in the contralateral unaffected breast is related to parity and estrogen-related genes. / Monahan, Denise A.; Wang, Jun; Lee, Oukseub; Revesz, Elizabeth; Taft, Nancy; Ivancic, David; Hansen, Nora M.; Bethke, Kevin P.; Zalles, C.; Khan, Seema A.

In: Surgical Oncology, Vol. 25, No. 4, 01.12.2016, p. 449-456.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cytologic atypia in the contralateral unaffected breast is related to parity and estrogen-related genes

AU - Monahan, Denise A.

AU - Wang, Jun

AU - Lee, Oukseub

AU - Revesz, Elizabeth

AU - Taft, Nancy

AU - Ivancic, David

AU - Hansen, Nora M.

AU - Bethke, Kevin P.

AU - Zalles, C.

AU - Khan, Seema A.

PY - 2016/12/1

Y1 - 2016/12/1

N2 - Purpose The contralateral unaffected breast (CUB) of women with unilateral breast cancer provides a model for the study of breast tissue-based risk factors. Using random fine needle aspiration (rFNA), we have investigated hormonal and gene expression patterns related to atypia in the CUBs of newly diagnosed breast cancer patients. Methods 83 women underwent rFNA of the CUB. Cytologic analysis was performed using the Masood Score (MS), atypia was defined as MS > 14. RNA was extracted using 80% of the sample. The expression of 20 hormone related genes was quantified using Taqman Low Density Arrays. Statistical analysis was performed using 2-tailed t tests and linear regression. Results Cytological atypia was more frequent in multiparous women (P = 0.0392), and was not associated with any tumor-related features in the affected breast. Masood Score was higher with shorter interval since last pregnancy (R = 0.204, P = 0.0417), higher number of births (R = 0.369, P = 0.0006), and estrogen receptor (ER) negativity of the index cancer (R = −0.203, P = 0.065). Individual cytologic features were associated with aspects of parity. Specifically, anisonucleosis was correlated with shorter interval since last pregnancy (R = 0.318, P = 0.0201), higher number of births (R = 0.382, P = 0.0004), and ER status (R = −0.314, P = 0.0038). Eight estrogen-regulated genes were increased in atypical samples (P < 0.005), including TFF1, AGT, PDZK1, PGR, GREB1, PRLR, CAMK2B, and CCND1. Conclusions Cytologic atypia, and particularly anisonucleosis, is associated with recent and multiple births and ER negative status of the index tumor. Atypical samples showed increased expression of estrogen-related genes, consistent with the role of estrogen exposure in breast cancer development.

AB - Purpose The contralateral unaffected breast (CUB) of women with unilateral breast cancer provides a model for the study of breast tissue-based risk factors. Using random fine needle aspiration (rFNA), we have investigated hormonal and gene expression patterns related to atypia in the CUBs of newly diagnosed breast cancer patients. Methods 83 women underwent rFNA of the CUB. Cytologic analysis was performed using the Masood Score (MS), atypia was defined as MS > 14. RNA was extracted using 80% of the sample. The expression of 20 hormone related genes was quantified using Taqman Low Density Arrays. Statistical analysis was performed using 2-tailed t tests and linear regression. Results Cytological atypia was more frequent in multiparous women (P = 0.0392), and was not associated with any tumor-related features in the affected breast. Masood Score was higher with shorter interval since last pregnancy (R = 0.204, P = 0.0417), higher number of births (R = 0.369, P = 0.0006), and estrogen receptor (ER) negativity of the index cancer (R = −0.203, P = 0.065). Individual cytologic features were associated with aspects of parity. Specifically, anisonucleosis was correlated with shorter interval since last pregnancy (R = 0.318, P = 0.0201), higher number of births (R = 0.382, P = 0.0004), and ER status (R = −0.314, P = 0.0038). Eight estrogen-regulated genes were increased in atypical samples (P < 0.005), including TFF1, AGT, PDZK1, PGR, GREB1, PRLR, CAMK2B, and CCND1. Conclusions Cytologic atypia, and particularly anisonucleosis, is associated with recent and multiple births and ER negative status of the index tumor. Atypical samples showed increased expression of estrogen-related genes, consistent with the role of estrogen exposure in breast cancer development.

KW - Anisonucleosis

KW - Breast cancer risk

KW - Contralateral unaffected breast

KW - Cytologic atypia

KW - Gene expression

KW - Random fine needle aspiration

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